Protein Summary

The crystal structure reveals 4 protomers in the asymmetric unit of the unit cell but the oligomeric form is monomeric. Size-exclusion chromatography supports a monomer as the significant solution state form.Each protomer has two domains including amino acids from ~1-138 and 201-242 in the first domain and residues 139-200 in the second domain (four-stranded beta-sheet).This protein has the annotation of an uncharacterized protein. PFAM has assigned this protein to the family of SAM-depenedent methyltransferases (PF08242/Methyltransf_12 and PF08241/Methyltransf_11). PSI-BLAST indicates hits with many hypothetical proteins and methyltransferases with the structure of the closest sequence homolog being the PDB id 1Y8C (S-adenosylmethionine-dependent methyltransferase from Clostridium Acetobutylicum ATCC 824). According to the FFAS server the most significant hits are with 1Y8C (Ref1)and 1WZN (SAM-dependent methyltransferase, Ref2) and 2AZT (Human Glycine N-methyltransferase, GNMT, Ref3) . The CDD (Conserved Domain Database) also indicates that the protein may have a UbiE domain which is is a methylase involved in ubiquinone/menaquinone biosynthesis.

Interestingly, the human glycine N-methyltransferase (2AZT, Ref3) is supposed to be a tetrameric enzyme which dissociates into compact monomers in the presence of 2-4M urea. Therefore, it may be possible that this protein may also display a non-monomeric oligomerization state under a different solution environment. A specific mutation in the 2AZT is associated with the disease hypermethioninaemia (elevated levels of methionine in serum resulting from inefficient metabolism of methionine) which can manifest itself in humans in the form of learning disabilities, mental retardation and other neurological problems and other symptoms or not be manifested at all.The structural superimposition of 2AZT (cyan) onto this protein is shown below:

For a review of human, mouse and rat glycine N-methytransferases, see Ref4. The active site in the GNMT is in the cavity between the two domains.